Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families.

Abstract:

:We have performed an extensive analysis of TP53 in 474 French families suggestive of Li-Fraumeni syndrome (LFS), including 232 families fulfilling the Chompret criteria. We identified a germline alteration of TP53 in 82 families (17%), in 67/232 of the families fulfilling the Chompret criteria (29%) and in 15/242 which did not fulfil these criteria (6%). Most of the alterations corresponded to missense mutations (67%), and we identified in four families genomic deletions removing the entire TP53 locus, the promoter and the non-coding exon 1, or exons 2-10. These results represent a definitive argument demonstrating that LFS results from TP53 haplodeficiency. The mean ages of tumour onset were significantly different between patients harbouring TP53 missense mutations and other types of alterations, missense mutations being associated with a 9 year earlier tumour onset. These results confirm that missense mutations not only inactivate p53 but also have an additional oncogenic effect. Germline alterations of TP53 that lead exclusively to loss of function are therefore associated with a later age of tumour onset and the presence of such mutations should be considered in atypical LFS families with tumours diagnosed after 40 years.

journal_name

J Med Genet

authors

Bougeard G,Sesboüé R,Baert-Desurmont S,Vasseur S,Martin C,Tinat J,Brugières L,Chompret A,de Paillerets BB,Stoppa-Lyonnet D,Bonaïti-Pellié C,Frébourg T,French LFS working group.

doi

10.1136/jmg.2008.057570

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

535-8

issue

8

eissn

0022-2593

issn

1468-6244

pii

jmg.2008.057570

journal_volume

45

pub_type

信件
  • Choanal atresia as a feature of ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome.

    abstract::We report here a father and daughter with digital abnormalities, nasolacrimal duct obstruction, and variable alopecia. The father had a cleft lip and palate and the daughter had choanal atresia. We propose they both have the EEC syndrome and show the variable expressivity of this disorder. Choanal atresia has not been...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.26.9.586

    authors: Christodoulou J,McDougall PN,Sheffield LJ

    更新日期:1989-09-01 00:00:00

  • Sweat testing to identify female carriers of X linked hypohidrotic ectodermal dysplasia.

    abstract::X linked hypohidrotic ectodermal dysplasia (XHED) affects many epithelial functions, including sweat gland formation. Female carriers who manifest XHED may have defective dentition or a patchy distribution of sweating or both, as determined by starch and iodine sweat testing. Such sweat testing can be useful in assign...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.28.5.330

    authors: Clarke A,Burn J

    更新日期:1991-05-01 00:00:00

  • Recurrence of the D409H mutation in Spanish Gaucher disease patients: description of a new homozygous patient and haplotype analysis.

    abstract::Gaucher disease results, in most patients, from mutations in the gene encoding glucocerebrosidase. Mutation D409H is the third most frequent in Spanish patients, accounting for 5.7% of all mutated alleles. This allele is associated mainly with the neurological forms of the disease. Recently, homozygosity for the D409H...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.35.9.775

    authors: Chabás A,Gort L,Montfort M,Castelló F,Domínguez MC,Grinberg D,Vilageliu L

    更新日期:1998-09-01 00:00:00

  • Monosomy 8p: an easily overlooked syndrome.

    abstract::Two patients with partial monosomy of the short arm of chromosome 8 are described. Their clinical features were very similar. Comparison with previously reported patients confirms the existence of an 8p- syndrome. The importance of cytogenetic investigations in all infants with major congenital heart defect and facial...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.23.2.153

    authors: Bröcker-Vriends AH,Mooij PD,van Bel F,Beverstock GC,van de Kamp JJ

    更新日期:1986-04-01 00:00:00

  • Extravillus dividing fetal cells at CVS: evidence of their erythroblastic origin.

    abstract::Cytological and cytogenetic studies were performed on nucleated fetal cells present in chorionic villus transport medium. The erythroblastic origin of these cells was shown. Fetal erythroblasts in spontaneous mitosis were frequently observed; chromosome counts were obtained from them but poor quality often prevented b...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.29.10.709

    authors: Terzoli G,Cartolano R,Rossella F,Cantù-Rajnoldi A,Brambati B,Fraccaro M,Simoni G

    更新日期:1992-10-01 00:00:00

  • Prenatal diagnosis of genetic disorders.

    abstract::Three hundred and fifty pregnancies were monitored by transabdominal amniocentesis in the fourteenth to sixteenth week of gestation followed by karyotyping or biochemica assays of cultured amniotic fluid cells and analysis of alpha-fetoprotein in the amniotic fluid supernatant. The pregnancy was interrupted in 36 case...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.13.3.182

    authors: Niermeijer MF,Sachs ES,Jahodova M,Tichelaar-Klepper C,Kleijer WJ,Galjaard H

    更新日期:1976-06-01 00:00:00

  • Mutation screening in British 21-hydroxylase deficiency families and development of novel microsatellite based approaches to prenatal diagnosis.

    abstract::21-hydroxylase deficiency is a recessively inherited disorder of steroidogenesis, resulting from mutations in the CYP21 gene. This 3.5 kb gene and a highly related CYP21P pseudogene reside on tandemly duplicated 30 kb segments of DNA in the class III HLA region, and the great majority of pathogenic mutations result fr...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:

    authors: Lako M,Ramsden S,Campbell RD,Strachan T

    更新日期:1999-02-01 00:00:00

  • Increased risk of cancer in patients with fumarate hydratase germline mutation.

    abstract::Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumour predisposition syndrome caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. The condition is characterised by predisposition to benign leiomyomas of the skin and the uterus, renal cell carcinoma (RCC), and uterine leiomyosar...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.2005.036400

    authors: Lehtonen HJ,Kiuru M,Ylisaukko-Oja SK,Salovaara R,Herva R,Koivisto PA,Vierimaa O,Aittomäki K,Pukkala E,Launonen V,Aaltonen LA

    更新日期:2006-06-01 00:00:00

  • Pathogenic variants in TNRC6B cause a genetic disorder characterised by developmental delay/intellectual disability and a spectrum of neurobehavioural phenotypes including autism and ADHD.

    abstract:BACKGROUND:Rare variants in hundreds of genes have been implicated in developmental delay (DD), intellectual disability (ID) and neurobehavioural phenotypes. TNRC6B encodes a protein important for RNA silencing. Heterozygous truncating variants have been reported in three patients from large cohorts with autism, but no...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmedgenet-2019-106470

    authors: Granadillo JL,P A Stegmann A,Guo H,Xia K,Angle B,Bontempo K,Ranells JD,Newkirk P,Costin C,Viront J,Stumpel CT,Sinnema M,Panis B,Pfundt R,Krapels IPC,Klaassens M,Nicolai J,Li J,Jiang Y,Marco E,Canton A,Latronico

    更新日期:2020-10-01 00:00:00

  • Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family.

    abstract:BACKGROUND:Primary pulmonary hypertension (PPH), resulting from occlusion of small pulmonary arteries, is a devastating condition. Mutations of the bone morphogenetic protein receptor type II gene (BMPR2), a component of the transforming growth factor beta (TGF-beta) family which plays a key role in cell growth, have r...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.37.10.741

    authors: Thomson JR,Machado RD,Pauciulo MW,Morgan NV,Humbert M,Elliott GC,Ward K,Yacoub M,Mikhail G,Rogers P,Newman J,Wheeler L,Higenbottam T,Gibbs JS,Egan J,Crozier A,Peacock A,Allcock R,Corris P,Loyd JE,Trembath RC,Nic

    更新日期:2000-10-01 00:00:00

  • Novel KIF7 mutations extend the phenotypic spectrum of acrocallosal syndrome.

    abstract:BACKGROUND:Acrocallosal syndrome (ACLS) is a rare recessive disorder characterised by corpus callosum agenesis or hypoplasia, craniofacial dysmorphism, duplication of the hallux, postaxial polydactyly, and severe mental retardation. Recently, we identified mutations in KIF7, a key component of the Sonic hedgehog pathwa...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmedgenet-2012-101016

    authors: Putoux A,Nampoothiri S,Laurent N,Cormier-Daire V,Beales PL,Schinzel A,Bartholdi D,Alby C,Thomas S,Elkhartoufi N,Ichkou A,Litzler J,Munnich A,Encha-Razavi F,Kannan R,Faivre L,Boddaert N,Rauch A,Vekemans M,Attié-Bitac

    更新日期:2012-11-01 00:00:00

  • The newly recognised limb/pelvis-hypoplasia/aplasia syndrome: report of a Bedouin patient and review.

    abstract::A Bedouin infant born to consanguineous parents and grandparents is reported. She had Müllerian aplasia and the phenotypic features of the limb/pelvis-hypoplasia/aplasia syndrome (MIM 276820). Phenotypic variability of this newly recognised syndrome is briefly discussed. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,评审

    doi:10.1136/jmg.30.1.62

    authors: Farag TI,al-Awadi SA,Marafie MJ,Bastaki L,al-Othman SA,Mohammed FM,AlSuliman IS,Murthy DS

    更新日期:1993-01-01 00:00:00

  • Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis.

    abstract:AIMS AND BACKGROUND:Mutations in the TARDBP gene, which encodes the TAR DNA binding protein (TDP-43), have been described in individuals with familial and sporadic amyotrophic lateral sclerosis (ALS). We screened the TARDBP gene in 285 French sporadic ALS patients to assess the frequency of TARDBP mutations in ALS. RE...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.2008.062463

    authors: Daoud H,Valdmanis PN,Kabashi E,Dion P,Dupré N,Camu W,Meininger V,Rouleau GA

    更新日期:2009-02-01 00:00:00

  • Epidermal mosaicism and Blaschko's lines.

    abstract::To test the hypothesis that epidermal rather than dermal mosaicism determines Blaschko's lines in hypomelanosis of Ito (HI), we studied the distribution of chromosomal mosaicism in four patients. In two, mosaicism had not been detected in lymphocytes or dermal fibroblasts, but was clearly shown in epidermal keratinocy...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.30.9.752

    authors: Moss C,Larkins S,Stacey M,Blight A,Farndon PA,Davison EV

    更新日期:1993-09-01 00:00:00

  • Map of 16 polymorphic loci on the short arm of chromosome 16 close to the polycystic kidney disease gene (PKD1).

    abstract::To define the PKD1 locus further, the gene involved in the most frequent form of adult polycystic kidney disease, probes from 16 polymorphic loci were mapped on 16p13.1-pter with the combined use of cell lines containing rearranged chromosomes and family studies. Five breakpoints in the distal part of 16p arbitrarily ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.27.10.603

    authors: Breuning MH,Snijdewint FG,Brunner H,Verwest A,Ijdo JW,Saris JJ,Dauwerse JG,Blonden L,Keith T,Callen DF

    更新日期:1990-10-01 00:00:00

  • Genetical components of physiological tremor.

    abstract::Pysiological tremor was measured in 14 pairs of monozygotic twins, 14 pairs of dizygotic twins, and 14 pairs of control subjects matched for age and sex. Postural finger tremor was measured in each pair using a sub-miniature accelerometer and subjecting the amplified signals to power spectral analysis. Significant gen...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.12.2.162

    authors: Tyrer PJ,Kasriel J

    更新日期:1975-06-01 00:00:00

  • Naevoid basal cell carcinoma syndrome and Charcot-Marie-Tooth disease: two autosomal dominant disorders segregating in a family.

    abstract::A family is described in which 16 individuals in 3 generations have Charcot-Marie-Tooth disease. At least 6 family members also have the naevoid basal cell carcinoma syndrome. In addition, 1 subject with both disorders has 2 young daughters with the naevoid basal cell carcinoma syndrome. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.15.4.288

    authors: Heimler A,Friedman E,Rosenthal AD

    更新日期:1978-08-01 00:00:00

  • Three single-nucleotide polymorphisms in LPA account for most of the increase in lipoprotein(a) level elevation in African Americans compared with European Americans.

    abstract:BACKGROUND:The extent which universally common or population-specific alleles can explain between-population variations in phenotypes is unknown. The heritable coronary heart disease risk factor lipoprotein(a) (Lp(a)) level provides a useful case study of between-population variation, as the aetiology of twofold higher...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.2006.042119

    authors: Chretien JP,Coresh J,Berthier-Schaad Y,Kao WH,Fink NE,Klag MJ,Marcovina SM,Giaculli F,Smith MW

    更新日期:2006-12-01 00:00:00

  • A new case of partial trisomy 19q (q13.2-->qter) owing to an unusual maternal translocation.

    abstract::A new case of trisomy 19q13.2-->qter is described in a male child which was caused by a maternal balanced translocation (13;19)(p13;q13.2). The major clinical features detected in the patient included the following: facial dysmorphism, bilateral coloboma, narrow and hypoplastic nails, cardiac malformations (Fallot's t...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.30.8.697

    authors: Valerio D,Lavorgna F,Scalona M,Conte A

    更新日期:1993-08-01 00:00:00

  • Sex reversal in a child with a 46,X,Yp+ karyotype: support for the existence of a gene(s), located in distal Xp, involved in testis formation.

    abstract::We report on a sex reversed Japanese child with a 46,X,Yp+ karyotype, minor dysmorphic features, and no testicular development. The Yp+ chromosome was derived by translocation of an Xp fragment (Xp21-Xp22.3) to Yp11.3. This has resulted in deletion of distal part of the Y chromosome pseudoautosomal region (DXYS15-telo...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.29.4.226

    authors: Ogata T,Hawkins JR,Taylor A,Matsuo N,Hata J,Goodfellow PN

    更新日期:1992-04-01 00:00:00

  • New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey.

    abstract::Bardet-Biedl syndrome (BBS) is an autosomal recessive condition characterised by rod-cone dystrophy, postaxial polydactyly, central obesity, mental retardation, hypogonadism, and renal dysfunction. BBS expression varies both within and between families and diagnosis is often difficult. We sought to define the conditio...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:

    authors: Beales PL,Elcioglu N,Woolf AS,Parker D,Flinter FA

    更新日期:1999-06-01 00:00:00

  • Porencephalic cyst in pycnodysostosis.

    abstract::We describe a case of pycnodysostosis with porencephaly and suggest an explanation for the porencephaly by a mechanism of imbalance between brain growth and its vascular supply and a normal but unopposed cerebrospinal fluid pressure. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.26.12.782

    authors: Figueiredo J,Reis A,Vaz R,Leáo M,Cruz C

    更新日期:1989-12-01 00:00:00

  • Biallelic mutations in CFAP65 cause male infertility with multiple morphological abnormalities of the sperm flagella in humans and mice.

    abstract:BACKGROUND:Male infertility is a prevalent issue worldwide, mostly due to the impaired sperm motility. Multiple morphological abnormalities of the sperm flagella (MMAF) present aberrant spermatozoa with absent, short, coiled, bent and irregular-calibre flagella resulting in severely decreased motility. Previous studies...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmedgenet-2019-106344

    authors: Li W,Wu H,Li F,Tian S,Kherraf ZE,Zhang J,Ni X,Lv M,Liu C,Tan Q,Shen Y,Amiri-Yekta A,Cazin C,Zhang J,Liu W,Zheng Y,Cheng H,Wu Y,Wang J,Gao Y,Chen Y,Zha X,Jin L,Liu M,He X,Ray PF,Cao Y,Zhang F

    更新日期:2020-02-01 00:00:00

  • Usher syndrome type I associated with bronchiectasis and immotile nasal cilia in two brothers.

    abstract::Usher syndrome type I is an autosomal recessive disease characterised by congenital sensorineural deafness, involvement of the vestibular system, and progressive visual loss owing to retinitis pigmentosa. Here we report the association of this disease with bronchiectasis, chronic sinusitis, and reduced nasal mucocilia...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.30.3.253

    authors: Bonneau D,Raymond F,Kremer C,Klossek JM,Kaplan J,Patte F

    更新日期:1993-03-01 00:00:00

  • Is geroderma osteodysplastica underdiagnosed?

    abstract::A girl with mild geroderma osteodysplastica is reported in order to raise the profile of this autosomal recessive condition which may be underdiagnosed. The important signs of this syndrome include a droopy, jowly face with a degree of malar hypoplasia and mandibular prognathism, lax, but non-hyperelastic skin, most m...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.25.12.854

    authors: Hunter AG

    更新日期:1988-12-01 00:00:00

  • Translocation X;13 in a patient with retinoblastoma.

    abstract::We describe the clinical and cytogenetic findings in a child with retinoblastoma and a translocation between chromosomes X and 13. The X;13 translocation in this patient does not involve band 13q14, the assigned locus for retinoblastoma. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.24.7.431

    authors: Ponzio G,Savin E,Cattaneo G,Ghiotti MP,Marra A,Zuffardi O,Danesino C

    更新日期:1987-07-01 00:00:00

  • Monozygotic twins concordant for congenital short femur.

    abstract::We report concordant male monozygotic twins with congenital short femur (proximal focal femoral deficiency) and discuss the aetiological implications. Coincidentally, they and their father have benign familial macrocephaly. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.23.4.363

    authors: Connor JM,Rae PS,Connor RA

    更新日期:1986-08-01 00:00:00

  • Correlation between FMR1 expression and clinical phenotype in discordant dichorionic-diamniotic monozygotic twin sisters with the fragile X mutation.

    abstract:BACKGROUND:The clinical phenotypes of females with fragile X full mutations vary drastically. Comparisons of discordant monozygotic twins provide opportunities to ascertain crucial factors that influence disease phenotype penetrance. OBJECTIVE:To identify crucial factors influencing the phenotypic expression of fragil...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmedgenet-2013-101978

    authors: Huang W,Luo S,Ou J,Zhu F,Xia Y,Xue J,Pan Q,Wu L,Duan R

    更新日期:2014-03-01 00:00:00

  • A proven de novo germline mutation in HNPCC.

    abstract::Hereditary non-polyposis colon cancer (HNPCC) is a heterogeneous group of tumour predisposition syndromes caused by germline mutations in at least four different mismatch repair genes. HNPCC patients are prone to the development of carcinomas of the intestinal tract and other specific sites. Identification of presumpt...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:

    authors: Kraus C,Kastl S,Günther K,Klessinger S,Hohenberger W,Ballhausen WG

    更新日期:1999-12-01 00:00:00

  • Novel CCM2 missense variants abrogating the CCM1-CCM2 interaction cause cerebral cavernous malformations.

    abstract:BACKGROUND:Cerebral cavernous malformations (CCMs) are vascular malformations mostly located within the central nervous system. Most deleterious variants are loss of function mutations in one of the three CCM genes. These genes code for proteins that form a ternary cytosolic complex with CCM2 as a hub. Very few CCM2 mi...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmedgenet-2019-106401

    authors: Bergametti F,Viot G,Verny C,Brechard MP,Denier C,Labauge P,Petit P,Nouet A,Viallet F,Chaussenot A,Hervé D,Tournier-Lasserve E,Riant F

    更新日期:2020-06-01 00:00:00